Orally dispersible tablet ( ODT) formulations of levo praziquantel ( L‐PZQ) and racemic PZQ (rac‐PZQ) are being developed to treat schistosomiasis in preschool‐aged children. Two crossover studies ( N = 32 and 36, respectively) assessed the relative bioavailability of these ODTs vs. Cysticide in adults. Bioavailability for L‐ PZQ of ODT rac‐ PZQ and Cysticide at 40 mg/kg was comparable (L‐ PZQ area under the concentration‐time curve from zero to infinity ( AUC 0–∞) test/reference ratio (90% confidence interval (CI)): 96% (84–111%)), whereas relative bioavailability of ODT L‐ PZQ 20 mg/kg was ~40% that of Cysticide 40 mg/kg (test/reference: 40% (35–46%)). AUC 0‐∞ and peak plasma concentration (C max) were highly variable in both studies. For both ODTs, L‐ PZQ AUC 0–∞ showed greater than dose‐proportional increase over the ranges tested and a significant food effect. Safety was comparable among formulations. The lower bioavailability of ODT L‐ PZQ, as well as the high variability and nondose‐proportionality of pharmacokinetic (PK) parameters, highlighted the need for a dedicated pediatric dose‐finding study for the selection of the most appropriate formulation and dose (L‐ PZQ ODT or rac‐ PZQ ODT).